Test pilots

Hope in motion:
Clinical trials propel medical advances

Christina Hennessy, Stamford Advocate

Christina Hennessy, Staff Writer

Published 7:11 pm, Tuesday, June 1, 2010

Dr Andrew Kenler stands in his Trumbull office with his patient, Judith Kudikoff of Bridgeport. Kenler ran a trial for a new treatment for breast cancer, which successfully treated Kudikoff.
Photo: B.K. Angeletti

Paul Calle of Stamford, an artist who worked with the NASA Art Program, recently completed a clinical trial for his advanced stage melanoma at the Bennett Cancer Center in Stamford. He is one of many people across the area and the country who each year participate in research studies aimed at developing better treatments, procedures and therapeutic interventions for people with cancer and other diseases.
Photo: Contributed Photo

Paul Calle of Stamford, an artist who worked with the NASA Art...

Dr Andrew Kenler sits in his Trumbull office with his patient, Judith Kudikoff of Bridgeport. Kenler ran a trial for a new treatment for breast cancer, which successfully treated Kudikoff.
Photo: B.K. Angeletti

Dr Andrew Kenler stands in his Trumbull office with his patient, Judith Kudikoff of Bridgeport. Kenler ran a trial for a new treatment for breast cancer, which successfully treated Kudikoff.
Photo: B.K. Angeletti

Dr Andrew Kenler sits in his Trumbull office with his patient, Judith Kudikoff of Bridgeport. Kenler ran a trial for a new treatment for breast cancer, which successfully treated Kudikoff.
Photo: B.K. Angeletti

Paul Calle has always been intrigued by exploration and adventure, by the people who ascended to the heavens and those who journeyed into uncharted lands on Earth.

His Stamford home is a reflection of these themes, captured in his drawings and paintings of America's early astronauts, as well as the explorers and traders who pushed into the American West in the 1800s.

As one of the first eight artists of the NASA Art Program, beginning in the early 1960s, he documented such milestone moments as Project Mercury, the first manned spaceflight; the 1969 moon landing and walk, and the Apollo 17 project that marked the last time a man walked on the moon. He is the artist who created the first man on the moon stamp.

It came to pass several years ago that Calle, 82, would face an equally uncharted path.

After being told he had noncurable, nonoperable metatastic melanoma, he was given the choice of participating in a clinical trial. At first, he wasn't interested. At the time, it had only been a short while since his wife of more than 50 years, Olga, had died.

"I thought the hell with it," he said, during a recent interview at his home.

But, after consulting with his three children, he opted to proceed. Perhaps his exploration into the unknown might go beyond his own battle.

"They said maybe I could help somebody."

As it turned out, soon after finishing a course with Ipilimumab, a drug being tested by Bristol-Myers Squibb, along with the standard chemotherapy treatment, his doctors discovered that the melanoma had gone.

Ipilimumab, which in Calle's case was administered intravenously, is an antibody that bolsters a person's immune system to fight cancer cells. The company earlier this year reported that it expected to launch the compound in several years, pending regulatory approval.

"Melanoma is a very difficult disease once it has spread," Del Prete said, noting that survival rates are low at advanced stages. It is the most dangerous and pervasive type of skin cancer, as it can quickly spread to other parts of the body.

For that reason, Calle is cautious.

"With melanoma, one never knows when it will come back," he said. "I did not beat it. I overcame it."

Over the years, the center's trials have helped to move drugs and therapies from experimental to established treatments. Aranesp, Avastin, Tarceva and Neulasta are just a few medications that were tested and eventually approved by the Federal Drug Administration, said Del Prete, who is the program's director. Some are used in the direct treatment of the cancer, some reduce or ameliorate the side effects of chemotherapy and radiation, and still others bolster the effectiveness of other drugs and treatments.

There are currently 90,229 trials going on in 172 countries, according to ClinicalTrials.gov, a website developed by the U.S. National Institutes of Health and other agencies to offer information on federally and privately supported clinical trials. In these trials, human volun teers test experimental treatments, substances or procedures; or they may explore new ways of using known therapies. As with other experiments, researchers test a particular theory and measure the outcome through data collection and analysis.

Not all clinical trials end in success. For some patients, the side effects prevent the full course of treatment, complications can develop (from severe to minor) or the treatment is not effective.

Clinical trials also look to establish new procedures and treatments that may be as good, if not better, than the current standard of care.

For instance, Dr. Andrew Kenler, a surgeon with Bridgeport Hospital, is testing a new way of treating early-stage invasive breast cancer that he said, if successful, could be a faster, less intrusive option for women who want to avoid traditional surgery. His Trumbull office, Park Avenue Surgical Associates, is one of only a few sites in the country conducting this trial. He currently is accruing patients for the trial.

"The treatment appears to be working," Kenler said of cryoablation, or cryosurgery, which kills cancer cells by freezing them in a relatively noninvasive procedure. "I am very optimistic based on what the pathology is showing."

For Judith Rudikoff, the fear brought on by the diagnosis of cancer has been tempered by hope, as the procedure has so far been a success.

"The most painful part was the Novocain," the Bridgeport resident said of the local anesthetic that was administered during the procedure. "I felt pressure, but absolutely no pain."

Her procedure lasted 20 minutes and took place in Kenler's office. She had already met all the pre-screening eligibility, which included having a tumor that measured less than an inch. On that day, Kenler inserted a probe, no larger than a small pen, through a small incision; then, guided by ultrasound technology, he directed the probe to the affected mass.

He then exposed the cancer cells, and a small area surrounding them, to extremely cold temperatures, minus 100 to minus 160 degrees centigrade. The tests so far have shown that the intense cold kills the cells.

But given this is experimental, Rudikoff also will undergo a lumpectomy (a surgical removal of the tumor and some surrounding tissue) and a course of radiation, which has been the established care for about a decade, Kenler said.

Not only does the conventional surgery and treatment provide a comparison, but it also allows researchers to test whether the cryoblation destroyed the cancer.

"This could be the great breakthrough," Kenler said.

Rudikoff said she made sure to do her homework prior to entering the trial. She asked questions, checked credentials, talked with her family and learned of the risks. And, after all that, she decided it was worth it to proceed.

Rudikoff said she is pleased her participation may now help others. With breast cancer in her family, it means her two daughters and five granddaughters may have greater options in the future.

"I generally support research," Rudikoff said. "That is how people have made previous discoveries."

Staff writer Christina Hennessy can be reached at Christina.hennessy@scni.com or 203-964-2241.

The event, which benefits Stamford Hospital's Bennett Cancer Center, offers participants a chance to honor survivors and to commemorate those who lost their fight against cancer.

It is hoped that participants will help to raise $1 million this year. The funds go toward the center's programs and services, such as its clinical trials program.

Dr. Salvatore Del Prete, the clinical trials program director, said the event goes a long way toward raising the funds that support the trials program, calling Hope in Motion, "instrumental."

Registration begins at 7 a.m. for all three events. The 50-mile bike ride sets off first in the morning, followed by the 5K run and finally the 5K walk. The event, which runs to 1:30 p.m., is open to individuals or teams.

When Dr. Richard Frank thinks about the progress made in terms of cancer care, clinical trials have certainly helped to get new treatments and therapies to patients.

"There is nothing to me more compelling as an oncologist as the fact that we are trying to increase the cure rate for cancer," said Frank, a hematologist-oncologist who since 2000 has been the director of cancer research at the Whittingham Cancer Center at Norwalk Hospital.

It means that in some cases, patients now have more than the standard, or conventional, treatment.

"It increases the options for the doctor," he said. "And, the more options we have for the patient, the better."

Still, there are drawbacks, which can be frustrating for doctors and patients, he said, such as long gaps from concept to the start of clinical trials.

"They also need to know that not all drugs pan out," he said. "And, some (therapies) have unintended consequences. It is a leap of faith."

The center works with patients to determine whether a trial is the proper course of treatment, officials said.

Those preliminary discussions would include information on eligibility requirements, the study's design, data collection requirements and potential side effects, said nurse practitioner Jennifer Long, who serves as the clinical coordinator.

All trial participants must sign an informed consent form before starting the screening process to determine whether they are eligible, Long said.

Frank and Long said as with any medical procedure or course of treatment, the first step is to talk with your doctor and discuss topics such as quality-of-life expectations and concerns about the treatment.

Throughout the study, patients are constantly assessed. Tracking the study is often a mix of administrative data collection and self-generated reports from the participants.

"There has been a great move toward electronic data capture," Long said. "There is a little less paper and pencil in the case of the report forms."

In terms of what constitutes a trial, it can vary.

For instance, there is an exercise study sponsored by Yale University that is recruiting for women with cancer who have completed therapy. The researchers will be comparing two different exercise programs and their effect on the participants, according to ClinicalTrails.gov, a clearinghouse website for information on clinical trials.

Frank said sometimes a pressing need will put a trial on a fast track. He offered as an example one that is testing a new drug for myelofibrosis, a bone marrow disorder.

"This is well ahead of schedule, because it is much needed. There is nothing out there right now," Frank said. "And, this appears to be a promising treatment."

Know the phases

When one describes a clinical trial, it typically is divided into three different phases, though there can be a fourth phase as well, according to the U.S. National Institutes of Health.

The following list comes from information on that agency's ClinicalTrials.gov Web site.

- Phase I -- This is the most experimental level when researchers are testing with a small group of people to assess the safety, to establish a safe dosage and to observe side effects.

- Phase II -- The number of participants increase as researchers further work to test the efficacy and safety of the drug, therapy or treatment.

- Phase III -- The pool of participants can increase tenfold as researchers look to confirm effectiveness, track side effects, compare to current standards of care and collect further information focused on the product's safety.

- Phase IV -- The work has now shifted to marketing studies to provide details about the risk factors of a particular drug, its benefits and its optimal use.